The effects of renal prostaglandins on medullary blood flow, active chloride transport, and antidiuretic hormone are important in urine dilution. It is surprising, therefore, that drugs that inhibit prostaglandin synthesis rarely cause hyponatremia. A patient in whom hyponatremia developed during ibuprofen administration is described and other reported cases of this association in adults are reviewed. The previous case reports fall into two well defined groups: first, neonates treated with indomethacin for patent ductus, and second, adults, often elderly, who usually have other diseases that impair urinary dilution. Although hyponatremia is a rare consequence of therapy with prostaglandin inhibitors, certain individuals are at increased risk and should be monitored for this side effect.